title: Congestive heart failure in rats is associated with increased collecting duct vasopressin sensitivity and vasopressin type 2 receptor reexternalization.
abstract: A number of studies have shown that rats with congestive heart failure (CHF) have increased protein levels of the vasopressin (AVP)-regulated water channel aquaporin-2 (AQP2) even during conditions with unchanged circulating levels of AVP, suggesting an increase in the sensitivity of the AVP type 2 (V2) receptor in experimental CHF. The present study was aimed at investigating AVP signaling in rats with moderate CHF (left ventricular end diastolic pressure >10 mmHg; normal plasma AVP levels) induced by ligation of the left anterior descending coronary artery. Sham-operated rats were used as controls. Western blotting analyses revealed an increased abundance of AQP2 in renal cortex (+33 ± 9% of sham; P < 0.05) and in inner medulla (IM) (+54 ± 15% of sham; P < 0.05) in CHF rats compared with sham-operated controls. Dose-response studies on isolated collecting ducts (CDs) showed an increased accumulation of cAMP in response to AVP in CHF rats compared with controls. V2 receptor surface-binding studies in isolated IMCDs showed a marked and comparable AVP-induced V2 receptor internalization in response to AVP in both CHF and control rats. As expected V2 receptor surface binding remained low after AVP challenge in control rats. In contrast to this, V2 receptor surface binding returned to pre-AVP levels within 30 min in the CHF rats, indicating an obtained recycling ability of the V2 receptor in CHF. Together the results indicate the presence of an increased AVP sensitivity in the CDs from CHF rats, associated with an acquired recycling ability of the V2 receptor.
authors.affiliation: Dept. of Biomedical Sciences, Univ. of Copenhagen, 3 Blegdamsvej, Bldg. 10.5, DK-2200 Copenhagen N, Denmark. Jonassen@sund.ku.dk.
authors.forename: Lone
authors.initials: L
authors.lastname: Brønd
authors.forename: Katrine M
authors.initials: KM
authors.lastname: Müllertz
authors.forename: Malene
authors.initials: M
authors.lastname: Torp
authors.forename: Jonas
authors.initials: J
authors.lastname: Nielsen
authors.forename: Martin
authors.initials: M
authors.lastname: Graebe
authors.forename: Niels
authors.initials: N
authors.lastname: Hadrup
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Sten
authors.initials: S
authors.lastname: Christensen
authors.forename: Thomas E N
authors.initials: TE
authors.lastname: Jonassen
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D001127:Arginine Vasopressin / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D007672:Kidney Cortex / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000378:metabolism*
chemical_list: D051399:Aquaporin 2; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000242:Cyclic AMP
keywords: aquaporin-2